The mammalian SWI/SNF (SWItch/Sucrose NonFermenting) complex is an evolutionarily well-conserved ATPase-powered chromatin-remodeling assembly composed of approximately 10 subunits. This complex (also known as the BRG1-associated factors (BAF) complex) coordinates the disruption of nucleosomes to permit the binding of various transcription factors, an activity crucial for proper differentiation and development (Kingston & Narlikar (1999) Genes Dev. 13:2339-2352; Vignali, et al. (2000) Mol. Cell. Biol. 20:1899-1910; Mohrmann & Verrizer (2005) Biochim. Biophys. Acta. 1681:59-73; Smith & Peterson (2005) Curr. Top. Dev. Biol. 65:115-148; de la Serna, et al. (2006) Nat. Rev. Genet. 6:461-473).
The entity known as the mammalian SWI/SNF complex is composed of a small series of compositionally distinct assemblies distinguished by the presence of alternative subunits. The choice of ARID (AT-rich interaction domain) family subunit (ARID1A or ARID1B) is a determinant of complexes with generally opposing roles in cell cycle control (Nagl, et al. (2007) EMBO J. 26:752-763; Blais & Dynlacht (2007) Curr. Opin. Cell Biol. 19:658-662). The complexes also contain either of two closely related alternative ATPases: human Brahma (BRM; Mohrmann & Verrijzer (2005) supra) or Brahma-related gene 1 (BRG1). Although BRM and BRG1 share a high degree of amino acid sequence identity, they are not equally important for development. Brg1-null mice die at a pre- or peri-implantation stage (Bultman, et al. (2000) Mol. Cell. 6:1287-1295), indicating a critical developmental role for BRG1. In contrast, Brm-null mice are viable and fertile, exhibiting only mild abnormalities that include a larger animal size and deregulated cell growth control in derived fibroblasts (Reyes, et al. (1998) EMBO J. 17:6979-6991). This study also showed an increased level of BRG1 in the animal tissues in the absence of BRM, and several studies indicate that BRG1- and BRM-containing SWI/SNF complexes play largely compensatory roles in cell cycle control (Strobeck, et al. (2002) J. Biol. Chem. 277:4782-4789; Klochendler-Yeivin, et al. (2002) Curr. Opin. Genet. Dev. 12:73-79; Roberts & Orkin (2004) Nat. Rev. Cancer. 4:133-142). Due to these phenotypes, it has been generally thought that BRM plays a similar but mostly auxiliary role to BRG1 in regulation of tissue-specific gene expression (de la Serna, et al. (2006) supra). However, few studies have compared the roles of BRM and BRG1 directly in differentiation models, and where considered (Griffin, et al. (2008) Development (Camb.) 135:493-500), BRM was generally confirmed as non-essential with relatively little other detail.